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The EJC component Magoh regulates proliferation and expansion of neural crest-derived melanocytes.
Dev Biol. 2013 Mar 15; 375(2):172-81.DB

Abstract

Melanoblasts are a population of neural crest-derived cells that generate the pigment-producing cells of our body. Defective melanoblast development and function underlies many disorders including Waardenburg syndrome and melanoma. Understanding the genetic regulation of melanoblast development will help elucidate the etiology of these and other neurocristopathies. Here we demonstrate that Magoh, a component of the exon junction complex, is required for normal melanoblast development. Magoh haploinsufficient mice are hypopigmented and exhibit robust genetic interactions with the transcription factor, Sox10. These phenotypes are caused by a marked reduction in melanoblast number beginning at mid-embryogenesis. Strikingly, while Magoh haploinsufficiency severely reduces epidermal melanoblasts, it does not significantly affect the number of dermal melanoblasts. These data indicate Magoh impacts melanoblast development by disproportionately affecting expansion of epidermal melanoblast populations. We probed the cellular basis for melanoblast reduction and discovered that Magoh mutant melanoblasts do not undergo increased apoptosis, but instead are arrested in mitosis. Mitotic arrest is evident in both Magoh haploinsufficient embryos and in Magoh siRNA treated melanoma cell lines. Together our findings indicate that Magoh-regulated proliferation of melanoblasts in the dermis may be critical for production of epidermally-bound melanoblasts. Our results point to a central role for Magoh in melanocyte development.

Authors+Show Affiliations

Genetic Disease Research Branch, National Human Genome Research Institute, Bethesda, MD 20892, USA. debra.silver@duke.eduNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, N.I.H., Intramural

Language

eng

PubMed ID

23333945

Citation

Silver, Debra L., et al. "The EJC Component Magoh Regulates Proliferation and Expansion of Neural Crest-derived Melanocytes." Developmental Biology, vol. 375, no. 2, 2013, pp. 172-81.
Silver DL, Leeds KE, Hwang HW, et al. The EJC component Magoh regulates proliferation and expansion of neural crest-derived melanocytes. Dev Biol. 2013;375(2):172-81.
Silver, D. L., Leeds, K. E., Hwang, H. W., Miller, E. E., & Pavan, W. J. (2013). The EJC component Magoh regulates proliferation and expansion of neural crest-derived melanocytes. Developmental Biology, 375(2), 172-81. https://doi.org/10.1016/j.ydbio.2013.01.004
Silver DL, et al. The EJC Component Magoh Regulates Proliferation and Expansion of Neural Crest-derived Melanocytes. Dev Biol. 2013 Mar 15;375(2):172-81. PubMed PMID: 23333945.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The EJC component Magoh regulates proliferation and expansion of neural crest-derived melanocytes. AU - Silver,Debra L, AU - Leeds,Karen E, AU - Hwang,Hun-Way, AU - Miller,Emily E, AU - Pavan,William J, Y1 - 2013/01/18/ PY - 2012/10/30/received PY - 2013/01/03/revised PY - 2013/01/04/accepted PY - 2013/1/22/entrez PY - 2013/1/22/pubmed PY - 2013/4/17/medline SP - 172 EP - 81 JF - Developmental biology JO - Dev. Biol. VL - 375 IS - 2 N2 - Melanoblasts are a population of neural crest-derived cells that generate the pigment-producing cells of our body. Defective melanoblast development and function underlies many disorders including Waardenburg syndrome and melanoma. Understanding the genetic regulation of melanoblast development will help elucidate the etiology of these and other neurocristopathies. Here we demonstrate that Magoh, a component of the exon junction complex, is required for normal melanoblast development. Magoh haploinsufficient mice are hypopigmented and exhibit robust genetic interactions with the transcription factor, Sox10. These phenotypes are caused by a marked reduction in melanoblast number beginning at mid-embryogenesis. Strikingly, while Magoh haploinsufficiency severely reduces epidermal melanoblasts, it does not significantly affect the number of dermal melanoblasts. These data indicate Magoh impacts melanoblast development by disproportionately affecting expansion of epidermal melanoblast populations. We probed the cellular basis for melanoblast reduction and discovered that Magoh mutant melanoblasts do not undergo increased apoptosis, but instead are arrested in mitosis. Mitotic arrest is evident in both Magoh haploinsufficient embryos and in Magoh siRNA treated melanoma cell lines. Together our findings indicate that Magoh-regulated proliferation of melanoblasts in the dermis may be critical for production of epidermally-bound melanoblasts. Our results point to a central role for Magoh in melanocyte development. SN - 1095-564X UR - https://www.unboundmedicine.com/medline/citation/23333945/The_EJC_component_Magoh_regulates_proliferation_and_expansion_of_neural_crest_derived_melanocytes_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0012-1606(13)00009-2 DB - PRIME DP - Unbound Medicine ER -